Related Experiment Video
Updated: Mar 16, 2026
07:51
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
1.3K
Sirtuin 3 Deregulation Promotes Pulmonary Fibrosis
Meredith L Sosulski1, Rafael Gongora1, Carol Feghali-Bostwick2
1Division of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana.
Summary
Reduced Sirtuin 3 (SIRT3) expression exacerbates pulmonary fibrosis by impairing antioxidant responses and promoting fibroblast differentiation. Restoring SIRT3 may offer a therapeutic strategy for this aging-related lung disease.
Area of Science:
- Mitochondrial Biology
- Cellular Aging
- Pulmonary Fibrosis Pathogenesis
Background:
- Oxidative stress drives alveolar epithelial cell injury and fibroblast-myofibroblast differentiation (FMD), central to pulmonary fibrosis (PF).
- Sirtuin 3 (SIRT3), a mitochondrial deacetylase, regulates antioxidant responses and mitochondrial homeostasis.
- Aging is associated with reduced SIRT3 expression and increased susceptibility to fibrotic diseases.
Purpose of the Study:
- To investigate the role of Sirtuin 3 (SIRT3) in the pathogenesis of pulmonary fibrosis (PF).
- To determine the impact of SIRT3 expression levels on oxidative stress and fibroblast-myofibroblast differentiation (FMD) in PF.
- To explore the therapeutic potential of modulating SIRT3 activity in PF.
Main Methods:
- Compared SIRT3 expression in lungs of young versus old mice and in murine models of PF.
- Analyzed SIRT3 staining in human PF lung tissues.
- Utilized murine PF models and human lung fibroblasts to assess the effects of SIRT3 modulation on oxidative stress markers, FMD, and SMAD3 signaling.
- Investigated the impact of resveratrol on SIRT3 expression and TGFβ1-induced changes.
Main Results:
- Reduced SIRT3 expression was observed in aged mice, PF models, and human PF lung tissues.
- Lower SIRT3 levels promoted TGFβ1-induced acetylation and inactivation of oxidative stress regulators (SOD2, IDH2) and enhanced FMD.
- SIRT3 overexpression attenuated TGFβ1-mediated FMD and reduced SMAD3 levels; resveratrol mimicked these effects.
- SIRT3-deficient mice exhibited increased susceptibility to PF and elevated SMAD3 expression.
Conclusions:
- SIRT3 plays a critical protective role against pulmonary fibrosis by maintaining mitochondrial function and suppressing pro-fibrotic signaling.
- A SIRT3/TGFβ1 interaction, potentially influenced by aging, contributes significantly to PF pathobiology.
- Targeting SIRT3 represents a promising therapeutic avenue for treating pulmonary fibrosis.
Related Concept Videos
01:16TGF - β Signaling Pathway
10.8K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K
01:20The JAK-STAT Signaling Pathway
13.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.7K
01:22PI3K/mTOR/AKT Signaling Pathway
6.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
6.1K
02:26NF-κB-dependent Signaling Pathway
10.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.2K